有机化学    

综述与进展

自由基介导的α-叔胺合成研究进展

方家恒a,b, 田润妍b, 陈继君b,*, 刘心元b,*   

  1. a哈尔滨工业大学化工与化学学院 哈尔滨 150001;
    b南方科技大学化学系 深圳格拉布斯研究院 南科大光明高等研究院 深圳 518055
  • 收稿日期:2024-06-27 修回日期:2024-07-10
  • 基金资助:
    国家自然科学基金(Nos. 22025103, 92256301, and 22331006)、广东省自然科学基金(2024A1515010325)和深圳市自然科学基金(JCYJ202205300115409020)资助项目.

Research Progress in the Synthesis of α-Tertiary Amines via Radical Strategies

Fang Jiahenga,b, Tian Runyanb, Chen Jijunb,*, Liu Xinyuanb,*   

  1. aSchool of Chemistry and Chemical Engineering, Harbin Institute of Technology, Harbin, 150001;
    bShenzhen Grubbs Institute, Department of Chemistry, and Guangming Advanced Research Institute, Southern University of Science and Technology, Shenzhen, 518055
  • Received:2024-06-27 Revised:2024-07-10
  • Contact: *E-mail: chenjj@sustech.edu.cn; liuxy3@sustech.edu.cn.
  • Supported by:
    National Natural Science Foundation of China (Nos. 22025103, 92256301, 22331006), the Natural Science Foundation of Guangdong Province of China (2024A1515010325), and the Shenzhen Science and Technology Program (JCYJ202205300115409020).

α-叔胺是一类在氮原子α位具有叔碳中心的胺类化合物. 由于叔碳中心的存在, α-叔胺在生物体内的脂溶性与代谢稳定性有所改变, 使其在药物研发领域具有重要的应用价值. 传统的α-叔胺合成方法包括: 酮亚胺的亲核加成、羰基化合物的亲电胺化、三级烯丙基亲电试剂的烯丙基胺化及重排反应等. 得益于自由基具有高活性、反应条件温和及良好的官能团兼容性, 自由基反应在合成α-叔胺方面表现出独特优势. 近年来, 发展出烯烃的自由基胺化/氢胺烷基化、自由基碳氮交叉偶联、亚胺的自由基加成、烷烃的碳氢键活化等方法. 本文综述了近十年来自由基介导的分子间α-叔胺合成方法, 并详细讨论了每种方法的特点.

关键词: α-叔胺, 自由基, 亚胺

α-Tertiary amines are a class of amine compounds with a tertiary carbon center at the α-position of the nitrogen atom. The presence of the tertiary carbon center significantly alters the lipid solubility and metabolic stability of α-tertiary amines in biological systems, making them valuable in pharmaceutical development. Traditional methods for the synthesis of α-tertiary amines include nucleophilic addition of ketimines, electrophilic amination of carbonyl compounds, allylic amination of tertiary allyl electrophiles, and rearrangement reactions. Due to the high reactivity, mild reaction conditions, and good functional group tolerance of the radical, radical reactions exhibit unique advantages in the synthesis of α-tertiary amines. Given the importance of α-tertiary amines and the advantages of radical reactions, various methods have been developed, including radical amination/hydroamination of alkenes, radical C-N cross-coupling, radical addition of imines, and C-H bond activation of alkanes. This review summarizes the radical-mediated intermolecular synthesis of α-tertiary amines over the past decade and discusses in detail the characteristics of each method.

Key words: α-tertiary amines, radical, imine